2-AMINOIMIDAZOLE DERIVATIVES AS A POTENTIAL ADJUVANT AGENT FOR MULTIDRUG-RESISTANT ACINETOBACTER BAUMANNII THROUGH ANTIBIOFILM AND ANTIBIOTIC RESENSITIZATION
DOI:
https://doi.org/10.53366/jimki.v8i3.229Keywords:
2-aminoimidazole, Acinetobacter baumannii, antibiofilm, antibiotic resensitization, antibiotic resistanceAbstract
Background: Antibiotic resistance in hospital-acquired infection (HAI) is a big problem for healthcare. It becomes worse by the trend of antibiotic resistance that is more common in gram-negative bacteria. Acinetobacter baumannii is a gram-negative bacteria that causes HAI and is considered multidrug-resistant. This trend raises the need for an agent to resensitize antibiotics. 2-aminoimidazole found in sea sponges Leucetta and Clathrina and rich in Indonesian seas is a potential agent to resensitize antibiotics in A. baumannii.
Methods: Literature searching worked using specific keywords in the search engine (Google and Google Scholar) and online databases (PubMed and SCOPUS). Twenty-three studies from various journals were retrieved.
Discussion: 2-AI has various derivative compounds followed by pharmacophores. 2-Aminoimidazole triazole (2-AIT) is one of the potential derivates with antibiofilm character to resensitize Acinetobacter baumannii. Optimization of the tail group 2-AIT carries out by several methods such as simple organic chemical reactions and Suzuki-Miyaura cross-coupling. The optimized group works as an antibiofilm by binding to the bfmR protein, which plays a role in forming biofilms. The toxicity of this compound in the hemolysis test and C. elegans is relatively low.
Conclusion: 2-AI has an antibiofilm activity that allows antibiotic diffusion in A. baumannii blocked by biofilm. This activity enables the resensitization of A. baumannii towards antibiotics. The safety of 2-AI has also been proven in vitro and in vivo. These findings conclude that 2-AI that extracted in sea sponges from Indonesian seas can be an agent to resensitize antibiotics in multidrug-resistant A. baumannii.
References
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13. Kim SY, Kim MH, Kim SI, Son JH, Kim S, Lee YC, et al. The sensor kinase BfmS controls production of outer membrane vesicles in Acinetobacter baumannii. BMC Microbiol. 2019 Dec 21;19(1):301.
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19. Reyes S, Iii RWH, Su Z, Simon ML, Melander C. Synthesis and biological activity of 2-aminoimidazole triazoles accessed by Suzuki–Miyaura cross-coupling. Organic & Biomolecular Chemistry. 2011;9(8):3041.
20. Su Z, Peng L, Worthington RJ, Melander C. Evaluation of 4,5-disubstituted-2-aminoimidazole-triazole conjugates for antibiofilm/antibiotic resensitization activity against MRSA and Acinetobacter baumannii. ChemMedChem. 2011;6(12):2243–51.
21. Bunders CA, Richards JJ, Melander C. Identification of aryl 2-aminoimidazoles as biofilm inhibitors in Gram-negative bacteria. Bioorganic & Medicinal Chemistry Letters. 2010;20(12):3797–800.
22. Milton ME, Minrovic BM, Harris DL, Kang B, Jung D, Lewis CP, et al. Re-sensitizing multidrug resistant bacteria to antibiotics by targeting bacterial response regulators: characterization and comparison of interactions between 2-aminoimidazoles and the response regulators bfmR from Acinetobacter baumannii and QseB from Francisella spp. Frontiers in Molecular Biosciences. 2018;5.
23. Stowe SD, Tucker AT, Thompson R, Piper A, Richards JJ, Rogers SA, et al. Evaluation of the toxicity of 2-aminoimidazole antibiofilm agents using both cellular and model organism systems. Drug and Chemical Toxicology. 2012;35(3):310–5.
2. O’Neill J. Review on antimicrobial resistance: tackling a crisis for the health and wealth of nations. London: Review on Antimicrobial Resistance; 2014. <https://amr-review.org/sites/default/files/AMR%20Review%20Paper%20-%20Tackling%20a%20crisis%20for%20the%20health%20and%20wealth%20of%20nations_1.pdf>
3. Hapsari AP, Wahyuni CU, Mudjianto D. Pengetahuan petugas surveilans tentang identifikasi healthcare-associated infections di Surabaya. Jurnal Berkala Epidemiologi. 2018 Aug 30;6(2):130-8.
4. Kurniawati AFS, Satyabakti P, Arbianti N. Perbedaan risiko multidrug resistance organisms (MDROs) menurut faktor risiko dan kepatuhan hand hygiene. Jurnal Berkala Epidemiologi. 2015 Sep 3;3(3):277-89.
5. Lee C, Lee JH, Park M, Park KS, Bae IK, Kim YB, et al. Biology of Acinetobacter baumannii: pathogenesis, antibiotic resistance mechanisms, and prospective treatment options. Front Cell Infect Microbiol. 2017 Mar 13;7:55.
6. Sutandhio S, Widodo ADW, Alimsardjono L, Wasito EB. Perbandingan distribusi dan pola kepekaan Acinetobacter baumannii terhadap antimikroba di RSUD Dr. Soetomo Surabaya periode Januari-Maret 2015, April-Juni 2015, dan Januari-Maret 2016. Jurnal Widya Medika Surabaya. 2018 Apr;4(1):18-23.
7. Mayasari E, Siregar C. Prevalence of Acinetobacter baumannii isolated from clinical specimens in Adam Malik Hospital. Majalah Kedokteran Andalas. 2014 Apr;37(1):1-7.
8. Karuniawati A, Saharman YR, Lestari DC. Detection of carbapenemase encoding genes in Enterobacteriace, Pseudomonas aeruginosa, and Acinetobacter baumannii isolated from patients at Intensive Care Unit Cipto Mangunkusumo Hospital in 2011. Acta Medica Indonesiana. 2013 Jan 1;45(2):101-6.
9. Eze EC, Chenia HY, Zowalaty MEE. Acinetobacter baumannii biofilms: effects of physicochemical factors, virulence, antibiotic resistance determinants, gene regulation, and future antimicrobial treatments. Infect Drug Resist. 2018 Nov 15;11:2277-99.
10. Yang C, Su P, Moi S, Chuang L. Biofilm formation in Acinetobacter baumannii: genotype-phenotype correlation. Molecules. 2019 May 14;24(10):1849.
11. Hassan WH, Al-Taweel AM, Proksch P. Two new imidazole alkaloids from Leucetta chagosensis sponge. Saudi Pharmaceutical Journal. 2009;17(4):295–8.
12. Russo TA, Manohar A, Beanan JM, Olson R, MacDonald U, Graham J, et al. The response regulator bfmR is a potential drug target for Acinetobacter baumannii. mSphere. 2016 May 11;1(3):1-19.
13. Kim SY, Kim MH, Kim SI, Son JH, Kim S, Lee YC, et al. The sensor kinase BfmS controls production of outer membrane vesicles in Acinetobacter baumannii. BMC Microbiol. 2019 Dec 21;19(1):301.
14. Pakharukova N, Tuittila M, Paavilainen S, Malmi H, Parilova O, Teneberg S, et al. Structural basis for Acinetobacter baumannii biofilm formation. Proc Natl Acad Sci U S A. 2018 May 22;115(21):5558-63.
15. Singh RP, Lovely CJ. The Leucetta alkaloids: synthetic aspects. Bioactive Natural Products Studies in Natural Products Chemistry. 2019;:43–79.
16. Koswatta PB, Lovely CJ. Structure and synthesis of 2-aminoimidazole alkaloids from Leucetta and Clathrina sponges. Nat Prod Rep. 2011;28(3):511–28.
17. Rogers SA, Bero JD, Melander C. Chemical synthesis and biological screening of 2-aminoimidazole-based bacterial and fungal antibiofilm agents. ChemBioChem. 2010;11(3):396–410.
18. Rogers SA, Huigens RW, Cavanagh J, Melander C. Synergistic effects between conventional antibiotics and 2-aminoimidazole-derived antibiofilm agents. Antimicrobial Agents and Chemotherapy. 2010Aug;54(5):2112–8.
19. Reyes S, Iii RWH, Su Z, Simon ML, Melander C. Synthesis and biological activity of 2-aminoimidazole triazoles accessed by Suzuki–Miyaura cross-coupling. Organic & Biomolecular Chemistry. 2011;9(8):3041.
20. Su Z, Peng L, Worthington RJ, Melander C. Evaluation of 4,5-disubstituted-2-aminoimidazole-triazole conjugates for antibiofilm/antibiotic resensitization activity against MRSA and Acinetobacter baumannii. ChemMedChem. 2011;6(12):2243–51.
21. Bunders CA, Richards JJ, Melander C. Identification of aryl 2-aminoimidazoles as biofilm inhibitors in Gram-negative bacteria. Bioorganic & Medicinal Chemistry Letters. 2010;20(12):3797–800.
22. Milton ME, Minrovic BM, Harris DL, Kang B, Jung D, Lewis CP, et al. Re-sensitizing multidrug resistant bacteria to antibiotics by targeting bacterial response regulators: characterization and comparison of interactions between 2-aminoimidazoles and the response regulators bfmR from Acinetobacter baumannii and QseB from Francisella spp. Frontiers in Molecular Biosciences. 2018;5.
23. Stowe SD, Tucker AT, Thompson R, Piper A, Richards JJ, Rogers SA, et al. Evaluation of the toxicity of 2-aminoimidazole antibiofilm agents using both cellular and model organism systems. Drug and Chemical Toxicology. 2012;35(3):310–5.
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2021-02-23
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2-AMINOIMIDAZOLE DERIVATIVES AS A POTENTIAL ADJUVANT AGENT FOR MULTIDRUG-RESISTANT ACINETOBACTER BAUMANNII THROUGH ANTIBIOFILM AND ANTIBIOTIC RESENSITIZATION. (2021). JIMKI: Jurnal Ilmiah Mahasiswa Kedokteran Indonesia, 8(3), 146-157. https://doi.org/10.53366/jimki.v8i3.229
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